Genetic Screening of the G2019S Mutation of the LRRK2 Gene in Southwest European, North African, and Sephardic Jewish Subjects

摘要

The G2019S mutation in exon 41 of the leucine-rich repeat kinase 2 (LRRK2) gene accounts for 3–6% of familial dominant Parkinson's disease (PD) and for 1–2% of sporadic PD. It seems that there is a north-south gradient of G2019S frequency in Europe in PD patients, and the frequency of the mutation is up to 41% in North African cases. To obtain a precise estimate of G2019S frequency in populations with relatively elevated incidence of mutation carriers, we have tested for the presence of the G2019S in the south Mediterranean countries. Three thousand one hundred healthy European subjects were compared for the G2019S incidence with 597 healthy Arab subjects originating from five populations in North Africa and with 361 healthy Sephardi Jews from five other populations. The main incidence of G2019S carriers is 1/46 in our sample of North African Arabs, the most elevated carrier incidence (1/30) being found in Moroccan Berbers. An elevated incidence (1/72) is also found in our sample of Sephardi Jews. These results contrast with the ones we found (1/1550) in a sample of 3100 healthy subjects originating from 15 populations of southern Europe. Six microsatellite markers were used in the 20 G2019S carriers we found, to conduct a haplotype analysis. Our finding on the elevated incidence of the G2019S mutation in North African Arabs and in Sephardi Jews, Berbers being the people where the mutation probably originates from, has some important consequences for future genetic diagnosis and counseling for PD in these populations